J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/02/767/10 $2.00
Volume 185, Number 4, February 17, 1997 767-776

CD45RC Isoforms Define Two Types of CD4 Memory T Cells, One of which Depends on Persisting Antigen

By Campbell Bunce and Eric B. Bell

From the Immunology Research Group, Biological Sciences, University of Manchester, Manchester M13 9PT, United Kingdom

The cellular basis of immunological memory remains a controversial area with respect to the identity of memory T cells and the role of persisting antigen. CD4 T cells are phenotypically divided by the expression of high and low molecular weight isoforms of CD45, surface markers that are frequently used to identify "naive" (CD45R^high) and "memory" (CD45R^low) subsets. The latter subset responds rapidly in antigen recall assays but paradoxically has a short life span, a property that is difficult to reconcile with long-term memory. The present study examines these issues using a DTH (delayed-type hypersensitivity) model in which contact sensitivity to dinitrochlorobenzene (DNCB) was transferred to athymic nude rats by recirculating CD4 T cell subsets defined in the rat by the anti-CD45RC mAb OX22. As expected, CD45RC⁺ (but not RC) CD4 T cells from normal unprimed rats transferred a DNCB-specific DTH response, whereas, 4 d after sensitization the CD45RC (memory) subset alone contained the DNCB reactivity. However, when donor cells were collected from thymectomized rats sensitized two mo earlier, DNCB-specific responses were transferred by both CD45RC and RC⁺ subsets suggesting that many of the latter had developed from cells with a memory phenotype. This was confirmed when CD45RC CD4 T cells from 4-d primed rats were parked in intermediate nude recipients and recovered 2 mo later. DNCB-specific activity was now found wholly within the CD45RC⁺ "revertant" subset; the CD45RC CD4 T cell population was devoid of activity. Importantly, we found that the total switch-back from CD45RC to RC⁺ could be prevented, apparently by persisting antigen. The results indicate that there are two functionally distinct categories of memory T cells: one, a short-lived CD45R^low type which orchestrates the rapid kinetics, the other, a longer-lived CD45R^high revertant which ensures that immunological memory endures.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Acosta, D. M., Arnaiz, M. R., Esteva, M. I., Barboza, M., Stivale, D., Orlando, U. D., Torres, S., Laucella, S. A., Couto, A. S., Duschak, V. G. (2008). Sulfates are main targets of immune responses to cruzipain and are involved in heart damage in BALB/c immunized mice. Int Immunol 20: 461-470 [Abstract] [Full Text]  
• Zaph, C., Rook, K. A., Goldschmidt, M., Mohrs, M., Scott, P., Artis, D. (2006). Persistence and Function of Central and Effector Memory CD4+ T Cells following Infection with a Gastrointestinal Helminth. J. Immunol. 177: 511-518 [Abstract] [Full Text]  
• Yang, C.-P., Sparshott, S. M., Duffy, D., Garside, P., Bell, E. B. (2006). The phenotype and survival of antigen-stimulated transgenic CD4 T cells in vivo: the influence of persisting antigen. Int Immunol 18: 515-523 [Abstract] [Full Text]  
• Sloma, C. R., Hansen, M. J., MacDougall, A. A., Van Keulen, V. P., Jenkins, R. B., Pease, L. R. (2005). A Class I Transgene Reveals Regulatory Events on Chromosome 1 Marking Peripheral T Cell Differentiation and Memory. J. Immunol. 174: 7564-7572 [Abstract] [Full Text]  
• Beeton, C., Pennington, M. W., Wulff, H., Singh, S., Nugent, D., Crossley, G., Khaytin, I., Calabresi, P. A., Chen, C.-Y., Gutman, G. A., Chandy, K. G. (2005). Targeting Effector Memory T Cells with a Selective Peptide Inhibitor of Kv1.3 Channels for Therapy of Autoimmune Diseases. Mol. Pharmacol. 67: 1369-1381 [Abstract] [Full Text]  
• Westermann, J., Bode, U., Sahle, A., Speck, U., Karin, N., Bell, E. B., Kalies, K., Gebert, A. (2005). Naive, Effector, and Memory T Lymphocytes Efficiently Scan Dendritic Cells In Vivo: Contact Frequency in T Cell Zones of Secondary Lymphoid Organs Does Not Depend on LFA-1 Expression and Facilitates Survival of Effector T Cells. J. Immunol. 174: 2517-2524 [Abstract] [Full Text]  
• Mizobuchi, T., Yasufuku, K., Zheng, Y., Haque, M. A., Heidler, K. M., Woods, K., Smith, G. N. Jr., Cummings, O. W., Fujisawa, T., Blum, J. S., Wilkes, D. S. (2003). Differential Expression of Smad7 Transcripts Identifies the CD4+CD45RChigh Regulatory T Cells That Mediate Type V Collagen-Induced Tolerance to Lung Allografts. J. Immunol. 171: 1140-1147 [Abstract] [Full Text]  
• Khan, N., Shariff, N., Cobbold, M., Bruton, R., Ainsworth, J. A., Sinclair, A. J., Nayak, L., Moss, P. A. H. (2002). Cytomegalovirus Seropositivity Drives the CD8 T Cell Repertoire Toward Greater Clonality in Healthy Elderly Individuals. J. Immunol. 169: 1984-1992 [Abstract] [Full Text]  
• Walzer, T., Arpin, C., Beloeil, L., Marvel, J. (2002). Differential In Vivo Persistence of Two Subsets of Memory Phenotype CD8 T Cells Defined by CD44 and CD122 Expression Levels. J. Immunol. 168: 2704-2711 [Abstract] [Full Text]  
• Zhai, Y., Shen, X.-D., Lehmann, M., Busuttil, R., Volk, H.-D., Kupiec-Weglinski, J. W. (2001). T Cell Subsets and In Vitro Immune Regulation in ""Infectious"" Transplantation Tolerance. J. Immunol. 167: 4814-4820 [Abstract] [Full Text]  
• Serbina, N. V., Flynn, J. L. (2001). CD8+ T Cells Participate in the Memory Immune Response to Mycobacterium tuberculosis. Infect. Immun. 69: 4320-4328 [Abstract] [Full Text]  
• Subra, J.-F., Cautain, B., Xystrakis, E., Mas, M., Lagrange, D., van der Heijden, H., van de Gaar, M.-J., Druet, P., Fournie, G. J., Saoudi, A., Damoiseaux, J. (2001). The Balance Between CD45RChigh and CD45RClow CD4 T Cells in Rats Is Intrinsic to Bone Marrow-Derived Cells and Is Genetically Controlled. J. Immunol. 166: 2944-2952 [Abstract] [Full Text]  
• Exton, M. S., Elfers, A., Jeong, W.-Y., Bull, D. F., Westermann, J., Schedlowski, M. (2000). Conditioned suppression of contact sensitivity is independent of sympathetic splenic innervation. Am. J. Physiol. Regul. Integr. Comp. Physiol. 279: R1310-R1315 [Abstract] [Full Text]  
• Pierson, T., Hoffman, T. L., Blankson, J., Finzi, D., Chadwick, K., Margolick, J. B., Buck, C., Siliciano, J. D., Doms, R. W., Siliciano, R. F. (2000). Characterization of Chemokine Receptor Utilization of Viruses in the Latent Reservoir for Human Immunodeficiency Virus Type 1. J. Virol. 74: 7824-7833 [Abstract] [Full Text]  
• Goldrath, A. W., Bogatzki, L. Y., Bevan, M. J. (2000). Naive T Cells Transiently Acquire a Memory-like Phenotype during Homeostasis-driven Proliferation. JEM 192: 557-564 [Abstract] [Full Text]  
• Ramirez, F., Mason, D. (2000). Recirculatory and Sessile CD4+ T Lymphocytes Differ on CD45RC Expression. J. Immunol. 165: 1816-1823 [Abstract] [Full Text]  
• Koetz, K., Bryl, E., Spickschen, K., O'Fallon, W. M., Goronzy, J. J., Weyand, C. M. (2000). T cell homeostasis in patients with rheumatoid arthritis. Proc. Natl. Acad. Sci. USA 97: 9203-9208 [Abstract] [Full Text]  
• Muraro, P. A., Pette, M., Bielekova, B., McFarland, H. F., Martin, R. (2000). Human Autoreactive CD4+ T Cells from Naive CD45RA+ and Memory CD45RO+ Subsets Differ with Respect to Epitope Specificity and Functional Antigen Avidity. J. Immunol. 164: 5474-5481 [Abstract] [Full Text]  
• Merica, R., Khoruts, A., Pape, K. A., Reinhardt, R. L., Jenkins, M. K. (2000). Antigen-Experienced CD4 T Cells Display a Reduced Capacity for Clonal Expansion In Vivo That Is Imposed by Factors Present in the Immune Host. J. Immunol. 164: 4551-4557 [Abstract] [Full Text]  
• Andersen, P., Smedegaard, B. (2000). CD4+ T-Cell Subsets That Mediate Immunological Memory to Mycobacterium tuberculosis Infection in Mice. Infect. Immun. 68: 621-629 [Abstract] [Full Text]  
• Luettig, B., Pape, L., Bode, U., Bell, E. B., Sparshott, S. M., Wagner, S., Westermann, J. (1999). Naive and Memory T Lymphocytes Migrate in Comparable Numbers Through Normal Rat Liver: Activated T Cells Accumulate in the Periportal Field. J. Immunol. 163: 4300-4307 [Abstract] [Full Text]  
• Saparov, A., Kraus, L. A., Cong, Y., Marwill, J., Xu, X.-Y., Elson, C. O., Weaver, C. T. (1999). Memory/effector T cells in TCR transgenic mice develop via recognition of enteric antigens by a second, endogenous TCR. Int Immunol 11: 1253-1264 [Abstract] [Full Text]  
• Nociari, M. M., Telford, W., Russo, C. (1999). Postthymic Development of CD28-CD8+ T Cell Subset: Age-Associated Expansion and Shift from Memory to Naive Phenotype. J. Immunol. 162: 3327-3335 [Abstract] [Full Text]  
• Ramage, J. M., Young, J. L., Goodall, J. C., Hill Gaston, J. S. (1999). T Cell Responses to Heat-Shock Protein 60: Differential Responses by CD4+ T Cell Subsets According to Their Expression of CD45 Isotypes. J. Immunol. 162: 704-710 [Abstract] [Full Text]  
• London, C. A., Perez, V. L., Abbas, A. K. (1999). Functional Characteristics and Survival Requirements of Memory CD4+ T Lymphocytes In Vivo. J. Immunol. 162: 766-773 [Abstract] [Full Text]  
• Boursalian, T. E., Bottomly, K. (1999). Stability of Naive and Memory Phenotypes on Resting CD4 T Cells In Vivo. J. Immunol. 162: 9-16 [Abstract] [Full Text]  
• Cerwenka, A., Carter, L. L., Reome, J. B., Swain, S. L., Dutton, R. W. (1998). In Vivo Persistence of CD8 Polarized T Cell Subsets Producing Type 1 or Type 2 Cytokines. J. Immunol. 161: 97-105 [Abstract] [Full Text]  
• De Boer, R. J., Noest, A. J. (1998). T Cell Renewal Rates, Telomerase, and Telomere Length Shortening. J. Immunol. 160: 5832-5837 [Abstract] [Full Text]  
• Basadonna, G. P., Auersvald, L., Khuong, C. Q., Zheng, X. X., Kashio, N., Zekzer, D., Minozzo, M., Qian, H.-Y., Visser, L., Diepstra, A., Lazarovits, A. I., Poppema, S., Strom, T. B., Rothstein, D. M. (1998). Antibody-mediated targeting of CD45 isoforms: A novel immunotherapeutic strategy. Proc. Natl. Acad. Sci. USA 95: 3821-3826 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS